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Research and Reports
Objectives: To determine (1) what percentage of ciprofloxacin regimens in community nursing facilities would meet criteria for unnecessary drug use and estimate the financial cost of this potentially unnecessary therapy to payers, and (2) to determine whether administration of drugs that may decrease ciprofloxacin absorption was more frequently associated with therapeutic failure than regimens in which this interaction was not present. Design: Multicenter, retrospective chart review. Setting: 10 community nursing facilities in central North Carolina. Patients: All nursing facility residents during a three-month period in 1994 (n = 1,040 residents) receiving ciprofloxacin for at least 48 hours (95 regimens in 87 residents). Main Outcome Measures: Percentage of regimens with indicators of unnecessary drug use, cost of potentially unnecessary drugs, coadministration of drugs containing multivalent cations (MVCs), and outcome of therapy. Results: 80 regimens (84%) met at least one of the criteria for unnecessary drug therapy. The cost of this potentially unnecessary therapy was estimated at $4,607, or 81% of the estimated total cost of ciprofloxacin therapy. No significant relationship was detected between the administration of ciprofloxacin with MVCs or nutritional supplements and failure of therapy. Conclusion: Ciprofloxacin use in nursing facilities could be improved considerably. An ongoing drug-use evaluation of quinolones and other high-cost antibiotics in nursing facilities should be used to enhance documentation and patterns of use. Additional studies are needed to determine whether these interventions are cost-effective and would result in improved outcomes. Key Words: Ciprofloxacin, Nursing facilities, Unnecessary drug use, Clinical outcomes, Pharmacoeconomics, Drug interactions Abbreviations Used: MVCs = multivalent cations; CFR = Code of Federal Regulations; UTI = urinary tract infection; CLcr = creatinine clearance; SD = standard deviation. Consult Pharm 1997; 12: 251-55. Antibiotics account for a substantial portion of drug expenditures in nursing facilities. The quinolone antibiotics are widely used in this setting because of their broad spectrum of activity and approved indications for common bacterial infections. These factors helped ciprofloxacin (Cipro, Bayer) rank fifth highest in drug sales to nursing facilities in the United States for the period March 1994 through March 1995.1 A growing body of literature suggests that ciprofloxacin and other antibiotics are often used inappropriately in long-term care patients, wasting scarce health care resources and increasing the risk of negative outcomes, including bacterial resistance.2 Monitoring antibiotic use is therefore critical to controlling medication expenditures and providing comprehensive pharmaceutical care. This monitoring presents a unique challenge for the consultant pharmacist, because antibiotics are usually used for only short periods of time, and therapy is often completed before regularly scheduled, monthly drug regimen review occurs. The purpose of this study was to determine what percentage of ciprofloxacin regimens in community nursing facilities would meet criteria for unnecessary drug use and estimate the financial cost of this potentially unnecessary therapy to payers. As part of our evaluation of therapy outcome, we sought to determine whether administration of drugs that may decrease ciprofloxacin absorption was associated with therapeutic failure more frequently than regimens in which this interaction was not present. Methods The records of all residents of 10 nursing facilities in central North Carolina receiving ciprofloxacin during a three-month period in 1994 were reviewed retrospectively for indicators of potentially unnecessary use. All residents receiving ciprofloxacin for more than 48 hours were included in the analysis. The definition of a potentially unnecessary drug as stated in ß42 CFR 483.420(a)(6) of the nursing home regulations, along with criteria used for evaluation of each definition are listed in Table 1. Table 1. Definitiona and Interpretationb of Unnecessary Drug "An unnecessary drug is any drug when used:
a From §42 CFR 483.420(a)(6). b From references 3 and 4. Indicators for unnecessary use were derived from a review of common infectious disease references.3,4 Data were recorded on standardized data sheets by one of two pharmacy students under the direct supervision of a consultant pharmacist. The students were collecting the data for drug-use and interaction-evaluation purposes; they were thus unaware of any intent for economic evaluation of the data. One of the authors (RWD) compiled the completed data sheets in a database. Results are reported in absolute numbers and percentage of all regimens. The cost of potentially unnecessary therapy was calculated on a fixed prescription reimbursement rate for Medicaid in North Carolina of:
(Average Wholesale Price - 10%) + $5.60 Cost of potentially unnecessary therapy is considered individually for each of the criteria to demonstrate potential financial savings in that area. Thus, a regimen could have been included as a whole or in part in more than one problem in Tables 3 through 5. This duplication was eliminated when calculating subtotal and total numbers and costs of potentially unnecessary therapy, so that the most any regimen could contribute to the subtotal or total cost of potentially unnecessary therapy was the cost of that regimen. We also conducted an analysis of association between coadministration of drugs containing multivalent cations (MVCs)-such as aluminum, magnesium, calcium, iron, or zinc-and outcome of therapy. All patients with documented outcomes were categorized into one of four groups:
Patients were further classified as either having responded to therapy or having failed therapy based on resolution of symptoms or laboratory indications of infection. These data were analyzed in a 2 x 4 contingency table and tested with chi-square analysis. Results A total of 95 ciprofloxacin regimens were identified in the 1,040 residents of the 10 nursing facilities. Demographic characteristics of the patients receiving ciprofloxacin and the prescribed regimens are listed in Table 2. The number of drug regimens meeting criteria for potentially unnecessary therapy secondary to indication, dosage, and duration are listed in Tables 3, 4, and 5, respectively. We also found six regimens with potentially suboptimal dosing based on our criteria: two cases of complicated urinary tract infection (UTI), three cases of respiratory infection, and one regimen for endocarditis. Additional therapy would have cost $35. Table 2. Demographics of Study Population and Regimens
Table 3. Regimens with Inadequate or Inappropriate Indications
b Number of regimens (and percentage of total regimens) that contained at least one of the above problems for inadequate or inappropriate indications. Table 4. Regimens with Inappropriate Dosing
b Number of regimens (and percentage of total regimens) that contained at least one of the above problems for inappropriate dosing Table 5. Regimens with Excessive Duration of Therapy
Of the regimens, 39 (41%) lacked documentation of outcome of therapy. Cost of these regimens was estimated at $2,482. Another 14 regimens (15%) noted only partial or no response to ciprofloxacin therapy. The cost of these 14 regimens was not included in the cost of unnecessary therapy unless other criteria were met that warranted inclusion. While a higher percentage of failures was noted in patients receiving MVCs within two hours of at least 50% of ciprofloxacin doses (45%) than in those receiving regimens without concurrent MVCs (30%), this difference was not statistically significant (p = 0.35, ß = 0.29). No adverse symptoms were attributed directly to ciprofloxacin therapy. Those adverse microbiologic events noted included seven episodes of bacterial overgrowth in which infection with resistant organisms was noted within 30 days of antibacterial therapy, and two episodes of reinfection within 30 days by bacteria of similar type and sensitivity to the original infecting organism. In all, 80 regimens (84%) met at least one criterion for unnecessary drug therapy. The cost of this potentially unnecessary therapy was estimated at $4,607, or 81% of the estimated total cost of therapy. Discussion In our survey, 84% of ciprofloxacin regimens met at least one criterion for unnecessary drug use. This includes 67 regimens (71%) that were potentially unnecessary based upon suboptimal indication, monitoring, or lack of documentation in these areas. Another 10 regimens were partially unnecessary based on excessive dose or duration of therapy. The cost of this therapy is substantial: 81% of the total cost of ciprofloxacin therapy. While many regimens may have suffered only from inadequate documentation rather than unnecessary use, the scope of this problem, together with the high use and cost of quinolone antibiotics, suggests closer monitoring is needed. These numbers, while high, are consistent with other reports. Pickering and associates5 found that only 25% of ciprofloxacin orders in a large, academic nursing facility were considered appropriate. Other authors have noted lack of documentation associated with antibiotic use of 31%-52%.6,7 Therefore, while inadequate documentation may constitute a large percentage of regimens meeting criteria for unnecessary drug use, suboptimal selection of antibiotics and dosing is a substantial problem. The lack of association between concurrent administration of ciprofloxacin with MVCs could be the result of other factors. We were able to find only 56 regimens with outcomes documented to evaluate this interaction. Therefore, because of our limited sample size, the power of this analysis is less than acceptable (71%). Most regimens were prescribed to treat UTI, which may not require as high a dose to achieve adequate urine concentrations to treat the infection. In our population, doses were generally higher, and treatment was often given for longer time periods than those necessary to treat UTI. Finally, because of the retrospective nature of this review, sampling bias could have occurred if more records for patients in any group were unavailable for review than in other groups. This could readily occur if patients receiving regimens with drug interactions failed therapy and, as a result, were not in the facility at the time of this review. Since serious therapeutic failures have been associated with this interaction,8 we reassert that quinolone antibiotics should not be administered with MVCs until additional studies are performed. Any interaction between quinolones and nutritional supplements has yet to be defined. As is true with any retrospective review, this study is limited by availability of patient information, lack of randomization, and reporting bias. We have already pointed out how lack of availability of patient records could have biased our results. However, one would deduce that this bias would be on the side of identifying fewer problems with therapy if patients were moved out of the facility secondary to failure or complications with ciprofloxacin therapy. Reporting bias, on the other hand, might be expected to introduce a greater percentage of problem outcomes rather than positive outcomes, as patients and health care professionals are more likely to note problems rather than lack of a problem. Lack of randomization could have affected the outcome of the interaction evaluation as well. However, because our sample size was insufficient, this issue remains unresolved. Conclusion Ciprofloxacin is widely used in nursing facilities. Closer monitoring of antibiotic use in this setting might ensure cost-effective therapy, optimize dosage and administration, and minimize bacterial resistance secondary to indiscriminate use. We recommend an ongoing drug-use evaluation of quinolones and other high-cost antibiotics to provide facilities and prescribers the interventions and retrospective data to improve patterns of antibiotic use. Because of the short-term duration of most antibiotic therapy, this drug-use evaluation program may need to be triggered by the initial antibiotic order to be effective. Administration of ciprofloxacin with MVCs may not result in a higher frequency of treatment failures in elderly patients treated for urinary tract infections, especially when ciprofloxacin is given in higher doses (i.e., 500 mg twice daily for 7 to 10 days); but larger studies are needed to evaluate this. Future studies should address what types of interventions are cost-effective in improving prescribing patterns and outcomes of antibiotic therapy in nursing facilities. References 1. Martin T. Miller Associates. Nursing home drug sales audit. 1995(Jan-Mar). 2. Rho JP, Yoshikawa TT. The cost of inappropriate use of anti-infective agents in older patients. Drugs Aging 1995; 6:263-7. 3. Hooper DC. Quinolones. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, Inc., 1995. 4. Sanford JP, Gilbert DN, Sande MA. The Sanford guide to antimicrobial therapy 1994. Dallas. Antimicrobial Therapy, Inc., 1994. 5. Pickering TD, Gurwitz JH, Zaleznik D, Noonan JP, Avorn J. The appropriateness of oral fluoroquinolone-prescribing in the long-term care setting. J Am Geriatr Soc 1994; 42:28-32. 6. Lee YL, Thrupp LD, Friis RH, Fine M, Maleki B, Cesario T. Nosocomial infections and antibiotic utilization in geriatric patients; a pilot prospective surveillance program in skilled nursing facilities. Gerontology 1992; 38:223-32. 7. Zimmer JG, Bentley DW, Valenti WM, Watson NM. Systemic antibiotic use in nursing homes a quality assessment. J Am Geriatr Soc 1986; 34:703-10. 8. Noyes M, Polk M. Norfloxacin and absorption of magnesium-aluminum. Ann Intern Med 1988; 109:168-9. Richard W. Druckenbrod, PharmD, BCPS, School of Pharmacy, Campbell University, Buies Creek, North Carolina; Todd King, PharmD, Neil Medical Group, Lillington, North Carolina; J. Edward Herring, PharmD, School of Pharmacy, Campbell University, Buies Creek, North Carolina. Address For Reprints: Richard W. Druckenbrod, PharmD, BCPS, Methodist Retirement Community, 2616 Erwin Rd., Durham, NC 27705.
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